Physicochemical Stimulus-Responsive Systems Targeted with Antibody Derivatives.

The application of monoclonal antibodies and antibody fragments with the advent of recombinant antibody technology has made notable progress in clinical trials to provide a regulated drug release and extra targeting to the special conditions in the function site. Modification of antibodies has facilitated using mAbs and antibody fragments in numerous models of therapeutic and detection utilizations, such as stimuli-responsive systems. Antibodies and antibody derivatives conjugated with diverse stimuli-responsive materials have been constructed for drug delivery in response to a wide range of endogenous (electric, magnetic, light, radiation, ultrasound) and exogenous (temperature, pH, redox potential, enzymes) stimuli. In this report, we highlighted the recent progress on antibody-conjugated stimuli-responsive and dual/multi-responsive systems that affect modern medicine by improving a multitude of diagnostic and treatment strategies.

Dietary antioxidants and liver enzymes in Rafsanjan, a Region in Southeast Iran.

Oxidative stress has been considered the main contributor to liver injury. Dietary antioxidants would be expected to improve liver function. The hepatoprotective effects of antioxidants are controversial. In the present study, the associations of some dietary antioxidants and the levels of serum liver enzymes were examined. This cross-sectional study was conducted using the Rafsanjan Cohort Study (RCS) data as a population-based prospective cohort which is a part of the Prospective Epidemiological Research Studies in IrAN (PERSIAN). A total of 9942 participants aged 35-70 years old were included in this study. Among this population, 4631 (46.59%) were male, and 5311 (53.42%) were female. Dietary intakes were collected by a validated food frequency questionnaire (FFQ) with 128 items. Aspartate transaminase (AST), Alanine transaminase (ALT), γ-glutamyl transferase (GGT), and Alkaline phosphatase (ALP) were measured by a biotecnica analyzer. Dichotomous logistics regression models were used to investigate the association between the elevated liver enzymes and intake of dietary antioxidants using crude and adjusted models. In the adjusted model, in subjects with higher consumption of Se, Vit A, Vit E, ß-carotene, α-carotene, and ß-cryptoxanthin, the odds ratios of elevated ALP were decreased compared to the reference group (ORs 0.79 (0.64-0.96), 0.80 (0.66-0.98), 0.73 (0.60-0.89), 0.79 (0.64-0.96), 0.78 (0.64-0.95), 0.80 (0.66-0.98), and 0.79 (0.64-0.98), respectively). Subjects with higher consumption of Se, Vit A, Vit E, and provitamin A carotenoids (ß-carotene, α-carotene, ß-cryptoxanthin) showed decreased odds of elevated ALP. These findings support the hypothesis that Se, Vit A, Vit E, and provitamin A carotenoids may be associated with improvements in ALP and act as suppressors against the development of liver injury.

Diagnostic and Therapeutic Applications of Exosome Nanovesicles in Lung Cancer: State-of-The-Art.

Lung cancer is a malignant disease with high morbidity, mortality, and poor prognosis since conventional therapeutic approaches are not sufficient. Recently, with the discovery of exosomes, researchers have implemented new approaches in the diagnosis and treatment of various malignancies such as lung cancer. Investigation of lung cancer cell-derived exosomes and analysis of their profile by advanced techniques will assist researchers to take advantage of the specific properties of these multivesicular bodies. Also, scientists have presented various encouraging methods in the treatment of lung cancer with loading drugs, proteins, microRNAs, and siRNAs inside specific antigen-targeted exosomes. This review discusses the role of exosomes as novel prognostic biomarkers (containing lipids, surface and internal proteins, miRNAs, and lncRNAs) and therapeutic agents (e.g. vaccine and targeted drug delivery systems) in lung cancer.

Evolution of hydrogels for cartilage tissue engineering of the knee: A systematic review and meta-analysis of clinical studies.

INTRODUCTION: In recent years, studies have boosted our knowledge about the biology and disorders of articular cartilage. In this regard, the design of hydrogel-based scaffolds has advanced to improve cartilage repair. However, the efficacy of knee cartilage repair using hydrogels remains unclear. The aim of systematic review and meta-analysis was to scrutinize the efficiency of hydrogel-based therapy in correcting cartilage defects of knee (femoral condyle, patella, tibia plateau and trochlea). METHODS: The search was conducted in PubMed to gather articles published from 2004/1/1 to 2019/10/01, addressing the effects of implant of hydrogel on knee joint cartilage regeneration. The Cochrane Collaboration's tool for estimating the risk of bias was applied to check the quality of articles. The clinical data for meta-analysis was recorded using the visual analog scale (VAS), Lysholm score, WOMAC, and IKDC. The guidelines of Cochrane Handbook for Systematic Reviews of Interventions were utilized to conduct the review and meta-analysis in the RevMan 5.3 software. RESULTS: The search resulted in 50 clinical trials that included 2846 patients, 986 of whom received cell-based hydrogel implants while 1860 patients used hydrogel without cell. There were significant differences comparing the pain scores based on the VAS (MD: -2.97; 95% CI: -3.15 to -2.79, P<0.00001) and WOMAC (MD: -25.22; 95% CI: -31.22 to -19.22, P<0.00001) between pre- and post-treatment with hydrogels. Furthermore, there were significant improvements in the functional scores based on the IKDC total score (MD: 30.67; P<0.00001) and the Lysholm knee scale (MD: 29.26; 95% CI: 26.74 to 31.78, P<0.00001). According to the Lysholm and IKDC score and after cumulative functional analysis, there was a significant improvement in this parameter (MD: 29.25; 95% CI: 27.26 to 31.25, P<0.00001). CONCLUSIONS: This meta-analysis indicated clinically and statistically significant improvements in the pain score (VAS and WOMAC) and the functional score (IKDC and Lysholm) after the administration of hydrogel compared to pretreatment status. So, the current evidence shows the efficiency of hydrogel-based therapy in correcting and repairing knee cartilage defects.

Ameliorative Effects of a Static Magnetic Field on Hyssop (Hyssopus officinalis L.) Growth and Phytochemical Traits Under Water Stress.

The present study was carried out in order to evaluate the promoting effect of a static magnetic field (SMF) on drought tolerance and medicinal properties in Hyssopus officinalis. In the current work, the effect of seed priming with SMF (45, 90, 200, and 250 mT for 5 min) was investigated in 60-day-old hyssop (H. officinalis) plants that were irrigated every 8 days. The assessments consisted of total dry mass, membrane integrity, photosynthetic pigment concentrations, polyphenol content, antioxidant enzyme activities, and antioxidant capacity. Compared with exclusively water stress, magnetopriming, particularly at 200 mT, significantly altered these parameters in the grown plants. At this intensity, the level of total dry mass, total chlorophyll, and polyphenol content increased by 94%, 2.5- and 7.7-fold, respectively. Also, the level of electrolyte leakage and malondialdehyde decreased by 35% and 33%. The reducing power, DPPH (1,1-diphenyl-2-picrylhydrozyl), and superoxide anion-scavenging activities were highly augmented as well. Magnetopriming at 200 mT increased catalase (+92%) and ascorbate peroxidase (+2.3-fold) activities. However, the highest activity of guaiacol peroxidase was recorded at 90 mT. Generally, the present study illustrated the positive effect of magnetopriming (200 mT) on improvement of drought tolerance in H. officinalis through protection of cellular membrane integrity, maintenance of photosynthetic pigment content, and alternation of antioxidant enzyme activities. Furthermore, the data showed this treatment (200 mT) not only had no negative effect on medicinal properties of H. officinalis, but also improved it via increasing total phenolic content and antioxidant capacity. Bioelectromagnetics. 2020;41:403-412. © 2020 Bioelectromagnetics Society.

Reducing effect of insulin resistance on alpha-synuclein gene expression in skeletal muscle.

BACKGROUND: Alpha-synuclein (SNCA) as the presynaptic protein is expressed in different tissues and prevents insulin-resistance (IR) through increasing glucose-uptake by adipocytes and muscles. However, the effect of insulin metabolism on SNCA expression has scarcely elucidated. In present study we assessed the probable effect of insulin resistance on SNCA expression in muscle C2C12 cells and also skeletal muscle tissues of type 2 diabetic mice. MATERIALS AND METHODS: Sixteen male C57BL/6 mice were divided into two experimental groups, including control and type 2 diabetic mice with IR (induced by high-fat diet + low-dose streptozotocin). The animals of the study involved the measurements of fasting blood glucose, oral-glucose-tolerance-test, as well as fasting plasma insulin. Moreover, insulin-resistant and insulin-sensitive muscle C2C12 cells were prepared. The insulin-resistance was confirmed by the glucose-uptake assay. Comparative quantitative real time PCR was used to assess the SNCA expression. RESULTS: The obtained results have showed a significant ~ 27% decrease in SNCA expression level in muscle tissue of diabetic mice (P = 0.022). Moreover, there was a significant change of SNCA expression in insulin-resistant C2C12 cells (P < 0.001). CONCLUSION: Type 2 diabetes due to insulin-resistance can decrease SNCA gene expression in muscles. In addition to the role of SNCA in cell susceptibility to insulin and glucose uptake, the SNCA expression can also be affected by insulin metabolism.

The role of fibromodulin in cancer pathogenesis: implications for diagnosis and therapy.

Fibromodulin (FMOD) is known as one of very important extracellular matrix small leucine-rich proteoglycans. This small leucine-rich proteoglycan has critical roles in the extracellular matrix organization and necessary for repairing of tissue in many organs. Given that the major task of FMOD is the modulation of collagen fibrillogenesis. However, recently observed that FMOD plays very important roles in the modulation of a variety of pivotal biological processes including angiogenesis, regulation of TGF-ß activity, and differentiation of human fibroblasts into pluripotent cells, inflammatory mechanisms, apoptosis and metastatic related phenotypes. Besides these roles, FMOD has been considered as a new tumor-related antigen in some malignancies such as lymphoma, leukemia, and leiomyoma. Taken together, these findings proposed that FMOD could be introduced as diagnostic and therapeutic biomarkers in treatment of various cancers. Herein, for first time, we highlighted the various roles of FMOD in the cancerous conditions. Moreover, we summarized the diagnostic and therapeutic applications of FMOD in cancer therapy.

Knockdown of sal-like 4 expression by small interfering RNA induces apoptosis in breast cancer cells.

Breast cancer is the most prevalent cancers worldwide and causes a significant amount of deaths annually. Spalt-like transcription factor 4 is known as a transcription factor, which has an important role in the proliferation of cancerous cells. Small interfering RNA (siRNA) is a short-chain molecule of 20 to 25 nucleotides that protrude on two sides of the 3', two nucleotides. In this study, using a specific sequence of siRNA against the sequence of this gene, its activity is investigated in the cell line of breast cancer. The breast cancer cells (MCF-7) were cultured and then, using a specific anti-sal-like 4 (SALL4) siRNA, their toxic doses were determined. Then, the gene is transfected into the cell. Proliferation and expression of the SALL4 and BCL-2 gene were measured using the real-time polymerase chain reaction method. The specific concentration of siRNA IC50 of the SALL4 gene was 40.35 nmole. Gene expression results indicated that the expression of the Bcl-2 gene in the siRNA group was significantly reduced ( P < 0.05). SiRNA can increase the apoptosis of breast cancer cells by reducing the gene expression of SALL4 gene and Bcl-2; it can be used as a novel targeted therapy. This strategy, in addition to increasing the specificity of the drug, also reduces the side effects when compared with conventional chemotherapy.

Stem cell- and gene-based therapies as potential candidates in Alzheimer's therapy.

Alzheimer's disease (AD) is a progressive neurodegenerative disorder, which is associated with impairments of memory, thinking, language, and reasoning. Despite extensive research aiming at the treatment of AD, durable and complete remissions are rare. Hence, new therapeutic approaches are required. Among various therapeutic approaches, stem cells (ie, neural stem cells, mesenchymal stem cells, and embryonic stem cells) and delivery of protective genes such as encoding nerve growth factor, APOE, and glial cell-derived neurotrophic factor have generated promise in AD therapy. Here, we summarized a variety of effective therapeutic approaches (ie, stem cells, and genes) in AD therapy.

Micro-RNAs as critical regulators of matrix metalloproteinases in cancer.

Metastasis is known to be one of the important factors associated with cancer-related deaths worldwide. Several cellular and molecular targets are involved in the metastasis process. Among these targets, matrix metalloproteinases (MMPs) play central roles in promoting cancer metastasis. MMPs could contribute toward tumor growth, angiogenesis, migration, and invasion via degradation of the extracellular matrix and activation of pre-pro-growth factors. Therefore, identification of various cellular and molecular pathways that affect MMPs could contribute toward a better understanding of the metastatic pathways involved in various tumors. Micro-RNAs are important targets that could affect MMPs. Multiple lines of evidence have indicated that deregulation of various micro-RNAs, including miR-9, Let-7, miR-10b, and miR-15b, affects metastasis of tumor cells via targeting MMPs.

Vitiligo and social acceptance.

BACKGROUND AND AIM: Vitiligo is a chronic skin disease characterized by a total or partial loss of melanocytes from the epidermis and other tissues of the skin. It is placed in the class of secondary psychiatric disorders and can also lead to psychological problems. The main aim of this study was to assess social acceptance in vitiligo patients. METHODS: This cross-sectional study was conducted on all of the patients (n=150) with vitiligo who were referred to dermatology clinics in Rafsanjan, Iran. The patients completed a social acceptability questionnaire (Marlowe-Crowne Social Desirability Scale), and information regarding their demographic characteristics was also collected. Data were gathered and analyzed with descriptive and inferential statistics using SPSS-19 software. RESULTS: The mean age of the patients was 27.56±10.53 years and 65.9% were female. Mean score of social acceptance among the patients was 13.51±7.08. The results showed that the mean scores of social acceptance were significantly lower in women, in those with single marital status, in those with face and neck lesions, and in those with disease duration less than 5 years. CONCLUSION: The results showed that certain groups of patients with vitiligo are at greater risk of experiencing lower social acceptance.

Physicochemical evaluation of sausages prepared by lantern fish (Benthosema pterotum) protein isolate.

The purpose of this study was to show how sausages produced with lantern fish (Benthosema pterotum) protein isolate at two levels 4% (sample A) and 2% (sample B), and then, the physicochemical and sensory properties of sausages (A and B) were determined during the storage (14, 30, and 60 days) at 4°C. Firstly, fish protein isolate (FPI) prepared at alkaline pH (12). It was found that the acidic value, peroxide value (PV), and thiobarbituric acid (TBA) value of sausages increased during the storage. The highest level of TBA value was found at the second month of storage as 0.51 mg malonaldehyde/kg. The PV and acidic value reached to 9.45 meq/kg and 4.82 at the end of storage, respectively. Moreover, the stiffness, adherence, and springiness were assessed by texture profile analysis which was found sausages containing FPI had stronger texture and structure compared to control sample. The SDS-PAGE analysis identified the proteins from 15.4 to 202.3 kDa, which exhibit no major differences in protein patterns of two types of sausages. Furthermore, sensory evaluation diagnostic was carried out in terms of the sensory attributes such as texture, flavor, odor, color, and overall acceptability, and the results indicated the greatest overall acceptability in samples containing 2% FPI.

Peganum Harmala (Aspand) Intoxication; a Case Report.

There are several reports in the literature indicating a great variety of pharmacological effects for peganum harmala or aspand such as sedative anti-bacterial, anti-fungal, antiviral and antiprotozoal. Some people believe that can be used for treatment of some organic or psychiatric disorders. We introduce a woman with history of long time constipation that was disappointed in novel medical treatment and decided to use comminuted Aspand to relieve her problem. Two hours after use, the intoxication symptoms manifested as blurred vision, phonophobia, floating feeling, and tinnitus ringing. Here we report the treatment process and outcome of this case.

Frequency of Anxiety in Patients With Drug Poisoning in Rafsanjan City, Iran, in 2013.

BACKGROUND: Expansion of technology and progression of sciences have led to wider access to agricultural and industrial drugs and chemicals, which has resulted in many problems. Both in wanted and unwanted ways people may take these toxic agents, which perhaps may be along with many unpredictable, life-threatening and mortal outcomes. Based on many studies, most of intentional poisonings arise from an origin of patients' psychological backgrounds, which confirms necessity and importance of the recent study. OBJECTIVES: This study aimed to study the prevalence of psychiatric disorders in patients with drug poisoning. PATIENTS AND METHODS: In this descriptive cross-sectional study, 116 cases of poisoning referred to emergency room of Ali-Ebn-Abitaleb Hospital in Rafsanjan city, Iran, were randomly selected. Frequency of anxiety among participants was evaluated through the Spielberger questionnaire. A past history of depression and obsession was also evaluated through interview by a psychiatrist based on diagnostic and statistical manual of mental disorders (DSM-5) criteria. All data were then collected and analyzed using SPSS version 17. RESULTS: Anxiety, as the second most common reason of psychiatric disorders in cases of poisoning, with a prevalence of 12.1% in form of mild, 75.9% moderate and 12.1% severe, was confirmed among the participants of this study. CONCLUSIONS: The prevalence of anxiety among cases of poisoning with both drugs and chemicals are noticeably higher than general population. This fact strongly suggests the necessity of in-advance consultation and treatment of any underlying psychiatric disorders of patients to prevent prospective complications.

Efficacy of life skills training on subjective well-being of students: a report from rafsanjan, iran.

OBJECTIVE: The aim was to investigate the efficacy of life skills training on subjective well-being (SWB) among high school females. METHODS: The population study comprised all female high school of Rafsanjan, Iran, in 2008-2009. Thirty students with the lowest scores according to the Molavi's SWB questionnaire were considered eligible. At the next stage, the required sample of 30 students were selected randomly and divided into two groups of experimental (15 subjects) and control (15 subjects). Then, life skills training sessions were started for the experimental group (eight sessions in a 4-week period). Control group did not receive any intervention. The method of data processing at a descriptive level was through using central tendency indicators, dispersion, frequency, and percentage. Student's t-test was used for analysis of independent variables. RESULTS: The greatest R(2) (0.48) was observed for SWB. The R(2) coefficients for neurosis, stress-depression, vitality, and life determination were 0.27, 0.15, 0.20, and 0.09, respectively. CONCLUSION: Life skills training showed the greatest effect regarding SWB of the students.

Essential Thrombocytosis Following Multiple Psychic Traumas.

The associations between exposure to traumatic events and psychiatric disorders such as posttraumatic stress disorder (PTSD), depression, and anxiety have been established. It is important that clinicians notice to this phenomenon and avoid from inappropriate interpretations and additional laboratory tests. Here, a case of 45-year-old man with Essential thrombocytosis developed after multiple psychic traumas was introduced.